tbuckley/cabot-search huggingface dataset:
1-year survival in haemophagocytic lymphohistiocytosis: a nationwide cohort study from England 2003–2018
Authors: Joe West, Peter Stilwell, Hanhua Liu, Lu Ban, Mary Bythell, Tim Card, Peter Lanyon, Vasanta Nanduri, Judith Rankin, Mark Bishton, Colin Crooks
Journal: Journal of Hematology & Oncology (2023)

Abstract Haemophagocytic lymphohistiocytosis (HLH) is a lethal syndrome of excessive immune activation. We undertook a nationwide study in England of all cases of HLH diagnosed between 2003 and 2018, using linked electronic health data from hospital admissions and death certification. We modelled interactions between demographics and comorbidities and estimated one-year survival by calendar year, age group, gender and comorbidity (haematological malignancy, auto-immune, other malignancy) using Cox regression. There were 1628 people with HLH identified. Overall, crude one-year survival was 50% (95% Confidence interval 48–53%) which varied substantially with age (0–4: 61%; 5–14: 76%; 15–54: 61%; &gt; 55: 24% p &lt; 0.01), sex (males, 46%, worse than females, 55% p &lt; 0.01) and associated comorbidity (auto-immune, 69%, haematological malignancy 28%, any other malignancy, 37% p &lt; 0.01). Those aged &lt; 54 years had a threefold increased risk of death at 1-year amongst HLH associated with malignancy compared to auto-immune. However, predicted 1-year survival decreased markedly with age in those with auto-immune (age 0–14, 84%; 15–54, 73%; &gt; 55, 27%) such that among those &gt; 55 years, survival was as poor as for patients with haematological malignancy. One-year survival following a diagnosis of HLH varies considerably by age, gender and associated comorbidity. Survival was better in those with auto-immune diseases among the young and middle age groups compared to those with an underlying malignancy, whereas in older age groups survival was uniformly poor regardless of the underlying disease process.
Pericardial late gadolinium enhancement and time to recurrence: a substudy from RHAPSODY, a phase 3 clinical trial of rilonacept in recurrent pericarditis
Authors: Paul C Cremer, David Lin, Sushil A Luis, John Petersen, Antonio Abbate, Christine L Jellis, Debbie Kwon, Antonio Brucato, Fang Fang, Antonella Insalaco, Martin LeWinter, Basil S Lewis, Liangxing Zou, Stephen J Nicholls, Allan L Klein, Massimo Imazio, John F Paolini, Antonio Abbate, Wael Abo-Auda, Asif Akhtar, Michael Arad, Shaul Atar, Bipul Baibhav, Karan Bhalla, Antonio Brucato, Sean Collins, David Colquhoun, Paul Cremer, David Cross, Girish Dwivedi, Alon Eisen, Nahum Freedberg, Shmuel Fuchs, Eliyazar Gaddam, Marco Gattorno, Eli Gelfand, Paul Grena, Majdi Halabi, David Harris, Massimo Imazio, Antonella Insalaco, Amin Karim, Allan Klein, Kirk Knowlton, Apostolos Kontzias, Robert Kornberg, Faisal Latif, David Leibowitz, Martin LeWinter, David Lin, Dor Lotan, Pey Wen Lou, S. Allen Luis, Mady Moriel, Stephen Nicholls, John Petersen, Michael Portman, Philip Roberts-Thomson, Elad Schiff, Robert Siegel, Michael Stokes, Paul Sutej, Samuel Wittekind, Valentin Witzling, Robert Zukermann
Journal:  (2023)

Abstract Aims In this protocol-predefined substudy of the RHAPSODY trial, the primary aim was to assess whether pericardial late gadolinium enhancement (LGE) was associated with time to pericarditis recurrence. Methods and results RHAPSODY was a Phase 3 double-blind, placebo-controlled, randomized-withdrawal trial that demonstrated the efficacy of rilonacept in recurrent pericarditis (RP). Patients with a history of multiple RP and an active recurrence were enrolled and had the option to participate in a cardiac magnetic resonance (CMR) imaging substudy. CMRs were interpreted by a blinded independent core laboratory with prespecified criteria to define pericardial LGE. Compared to patients with trace or mild pericardial LGE (n = 9), patients with moderate or severe pericardial LGE (n = 16) generally had a higher number of recurrent episodes per year (5.3 vs. 3.9) and a higher mean CRP level (3.6 vs. 1.1 mg/dL). Overall, 10/14 (71.4%) who received a placebo had a recurrence compared to 0/11 (0%) who received rilonacept. In patients randomized to placebo who had moderate or severe pericardial LGE, the median time to recurrence was 4.2 weeks compared to 10.7 weeks in patients who had trace or mild pericardial LGE. At the conclusion of the event-driven randomized-withdrawal period, among patients receiving a placebo, 5/7 (71.4%) with trace or mild pericardial LGE and 5/7 (71.4%) with moderate or severe pericardial LGE had a recurrence. Conclusions Among patients with multiple RP, these preliminary findings support the concept of pericardial LGE as an imaging biomarker that may inform the duration of treatment and risk of recurrence with cessation of therapy and larger studies should be considered. ClinicalTrials.gov Identifier NCT03737110
Predicting and overcoming resistance to CDK9 inhibitors for cancer therapy
Authors: Chen Hu, Lijuan Shen, Fengming Zou, Yun Wu, Beilei Wang, Aoli Wang, Chao Wu, Li Wang, Jing Liu, Wenchao Wang, Qingsong Liu
Journal: Acta Pharmaceutica Sinica B (2023)

Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival. Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers. However, the study and knowledge on drug resistance to CDK9 inhibitors are very limited. In this study, we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152. Through genomic sequencing, we identified in the kinase domain of CDK9 a mutation L156F, which is also a coding SNP in the CDK9 gene. By knocking in L156F into cancer cells using CRISPR/Cas9, we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors, not only ATP competitive inhibitor but also PROTAC degrader. Mechanistically, CDK9 L156F disrupts the binding with inhibitors due to steric hindrance, further, the mutation affects the thermal stability and catalytic activity of CDK9 protein. To overcome the drug resistance mediated by the CDK9-L156F mutation, we discovered a compound, IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant. Together, we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.
Sarcopenic obesity in free-living older adults detected by the ESPEN-EASO consensus diagnostic algorithm: Validation in an Italian cohort and predictive value of insulin resistance and altered plasma ghrelin profile
Authors: Gianluca Gortan Cappellari, Annamaria Semolic, Michela Zanetti, Pierandrea Vinci, Mario Ius, Gianfranco Guarnieri, Luca Busetto, Lorenzo Maria Donini, Rocco Barazzoni
Journal: Metabolism (2023)
Reply to Zhipeng Mai, Weigang Yan, and Zhien Zhou’s Letter to the Editor re: Gabriela Ilie, Ricardo Rendon, Ross Mason, et al. A Comprehensive 6-mo Prostate Cancer Patient Empowerment Program Decreases Psychological Distress Among Men Undergoing Curative Prostate Cancer Treatment: A Randomized Clinical Trial. Eur Urol 2023;83:561–70
Authors: Gabriela Ilie, Robert D.H. Rutledge
Journal: European Urology (2023)
A step-by-step approach for selecting an optimal minimal important difference
Authors: Yuting Wang, Tahira Devji, Alonso Carrasco-Labra, Madeleine T King, Berend Terluin, Caroline B Terwee, Michael Walsh, Toshi A Furukawa, Gordon H Guyatt
Journal: BMJ (2023)

Researchers have proposed that the minimal important difference (MID), the smallest change or difference that patients perceive as important, could aid the interpretation of patient reported outcomes measure (PROM) scores. When multiple MIDs for a given PROM differ substantially, the selection of an optimal MID to aid interpretation could prove challenging. This article describes a systematic, step-by-step selection approach developed to resolve this problem. An optimal MID, at least, should be methodologically sound and should, as far as possible, match the intended application contexts. Therefore, this approach is geared to explaining the variability of the MIDs for the PROM of interest by the methodological rigor and contextualised factors influencing the MID application, and where appropriate, provides one optimal MID (ie, the median of the selected estimates in a relatively narrow range).
Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias
Authors: Ricardo de Matos Simoes, Ryosuke Shirasaki, Sondra L. Downey-Kopyscinski, Geoffrey M. Matthews, Benjamin G. Barwick, Vikas A. Gupta, Daphné Dupéré-Richer, Shizuka Yamano, Yiguo Hu, Michal Sheffer, Eugen Dhimolea, Olga Dashevsky, Sara Gandolfi, Kazuya Ishiguro, Robin M. Meyers, Jordan G. Bryan, Neekesh V. Dharia, Paul J. Hengeveld, Johanna B. Brüggenthies, Huihui Tang, Andrew J. Aguirre, Quinlan L. Sievers, Benjamin L. Ebert, Brian J. Glassner, Christopher J. Ott, James E. Bradner, Nicholas P. Kwiatkowski, Daniel Auclair, Joan Levy, Jonathan J. Keats, Richard W. J. Groen, Nathanael S. Gray, Aedin C. Culhane, James M. McFarland, Joshua M. Dempster, Jonathan D. Licht, Lawrence H. Boise, William C. Hahn, Francisca Vazquez, Aviad Tsherniak, Constantine S. Mitsiades
Journal: Nature Cancer (2023)
Detection of crystals in joint fluid aspirates with polychromatic polarisation microscopy
Authors: Husam Jum'ah, Michael Shribak, Adib Keikhosravi, Bin Li, Yuming Liu, Deya Obaidat, Kevin W Eliceiri, Agnes Loeffler, Salman Ayub
Journal: Annals of the Rheumatic Diseases (2023)
Debunking Sex and Disentangling Gender From Oncology
Authors: Ash B. Alpert, Lexis Rivers, Charlie Manzano, Roman Ruddick, Spencer Adams, Juno Obedin-Maliver, R. Donald Harvey, Jennifer J. Griggs, Don Operario
Journal: Journal of Clinical Oncology (2023)

Ontological OppressionThe construction of otherness because of assumptions about personhood-otherwise known as ontological oppression 1 -excludes or misrepresents bodies or identities on the basis of preset categories.Ontologic constructs of gender in oncology encompass the notions that gender is inseparable from and synonymous with sex assigned at birth (henceforth sex), that gender is a static social concept across history or a fixed identity across the personal life course, and that sex is an objective and fixed category that can be easily assessed by a clinician.In addition to sex being conflated with gender, sex is used to make assumptions about a person's anatomy, chromosomes, and/or endogenous hormones. 2 The presence of transgender and intersex people therefore challenges unquestioned assumptions and conflated concepts that are pervasive in medicine and particularly salient in oncology for several reasons.First, discourses regarding specific cancers (eg, ovarian, endometrial, prostate) are often conflated with gender.Second, cancer epidemiology is often linked to a conflated sex/gender marker (eg, breast cancer incidence described specifically for women or men).Third, oncology subspecialty care is often gendered, and in the context of cancer treatment, occupying exclusively gendered spaces may be particularly painful.Last, mistakes regarding laboratory values or chemotherapeutic dosing may be particularly hazardous.Conflated conceptions of bodies and selfhood are interwoven throughout oncology training, algorithms, and epidemiological and other biomedical analyses.Cancer epidemiology (eg, women have higher rates of cholangiocarcinoma than men), differential diagnoses, and many other core aspects of oncology rely on conflated concepts of gender and anatomy.These conflations render invisible and pathologic transgender and intersex people whose anatomy, chromosomes, or hormones do not match categorical expectations.Such ontological oppression has many consequences including stigma and substandard care.This analytic essay, authored by queer and transgender academic clinicians, researchers, nonacademic community members, and allies, proposes a systems-based approach to degendering oncology, which we define as the conscious and explicit disentangling of gender, anatomy, hormonal milieu, karyotype and other biological factors in oncologic diagnoses, epidemiological analysis, and knowledge production along with eliminating sex from our conceptual framework of bodies and disease.We provide examples of the implementation of degendering oncology, including steps that can be taken immediately by clinicians, researchers, and administrators.
Maladaptive TGF-β Signals to the Alveolar Epithelium Drive Fibrosis after COVID-19 Infection
Authors: Changfu Yao, Tanyalak Parimon, Milena S. Espindola, Miriam S. Hohmann, Bindu Konda, Cory M. Hogaboam, Barry R. Stripp, Peter Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Maladaptive TGF-β Signals to the Alveolar Epithelium Drive Fibrosis After COVID-19 Infection." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Intent Matters: Real-World Applicability of Idecabtagene Vicleucel Usage in the United States
Authors: Rajshekhar Chakraborty, Samer Al Hadidi
Journal: Journal of Clinical Oncology (2023)

Hansen et al 1 published a retrospective cohort study highlighting, to our knowledge, the first report on real-world outcomes with idecabtagene vicleucel (ide-cel) in relapsed/ refractory (R/R) multiple myeloma (MM).Currently, we have two approved chimeric antigen receptor (CAR) T-cell therapies in R/R MM: ide-cel and ciltacabtagene autoleucel (cilta-cel).Since patients enrolled in clinical trials with strict inclusion/ exclusion criteria may not be representative of an average patient in clinical practice, such data are extremely valuable to examine any potential gap between efficacy and effectiveness.However, we have a few concerns regarding reporting of the efficacy data in this study.
Impact of <sup>18</sup>F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Versus Conventional Staging in Patients With Locally Advanced Breast Cancer
Authors: Ian S. Dayes, Ur Metser, Nicole Hodgson, Sameer Parpia, Andrea F. Eisen, Ralph George, Phillip Blanchette, Tulin D. Cil, Angel Arnaout, Adrien Chan, Mark N. Levine
Journal: Journal of Clinical Oncology (2023)

PURPOSE Patients with locally advanced breast cancer (LABC) typically undergo staging tests at presentation. If staging does not detect metastases, treatment consists of curative intent combined modality therapy (neoadjuvant chemotherapy, surgery, and regional radiation). Positron emission tomography-computed tomography (PET-CT) may detect more asymptomatic distant metastases, but the evidence is based on uncontrolled studies. METHODS For inclusion, patients had histological evidence of invasive ductal carcinoma of the breast and TNM stage III or IIb (T3N0, but not T2N1). Consenting patients from six regional cancer centers in Ontario were randomly assigned to 18 F-labeled fluorodeoxyglucose PET-CT or conventional staging (bone scan, CT of the chest/abdomen and pelvis). The primary end point was upstaging to stage IV. A key secondary outcome was receiving curative intent combined modality therapy (ClinicalTrials.gov identifier: NCT02751710 ). RESULTS Between December 2016 and April 2022, 184 patients were randomly assigned to whole-body PET-CT and 185 patients to conventional staging. Forty-three (23%) PET-CT patients were upstaged to stage IV compared with 21 (11%) conventional staged patients (absolute difference, 12.3% [95% CI, 3.9 to 19.9]; P = .002). Consequently, treatment was changed in 35 (81.3%) of 43 upstaged PET-CT patients and 20 (95.2%) of the 21 upstaged conventional patients. Subsequently, 149 (81%) patients in the PET-CT group received combined modality treatment versus 165 (89.2%) patients in the conventional staging group (absolute difference, 8.2% [95% CI, 0.1 to 15.4]; P = .03). CONCLUSION In patients with LABC, PET-CT detected more distant metastases than conventional staging, and fewer PET-CT patients received combined modality therapy. Our randomized trial demonstrates the utility of the PET-CT staging strategy.
Re: Gabriela Ilie, Ricardo Rendon, Ross Mason, et al. A Comprehensive 6-mo Prostate Cancer Patient Empowerment Program Decreases Psychological Distress Among Men Undergoing Curative Prostate Cancer Treatment: A Randomized Clinical Trial. Eur Urol. 2023;83:561–70
Authors: Zhipeng Mai, Weigang Yan, Zhien Zhou
Journal: European Urology (2023)
A case-control pharmacovigilance study of TNF-alpha inhibitors and interleukin inhibitors on tuberculosis, Candida, lymphoma and suicidality using the FAERS database (2014-2020)
Authors: Domenico Arcuri, Mohammed Kaouache, François Lagacé, Denis Sasseville, Ivan Litvinov
Journal: Journal of the American Academy of Dermatology (2023)
Exhaustion-associated cholesterol deficiency dampens the cytotoxic arm of antitumor immunity
Authors: Chengsong Yan, Lin Zheng, Shutan Jiang, Haochen Yang, Jun Guo, Lu-yi Jiang, Tongzhou Li, Haosong Zhang, Yibing Bai, Yu Lou, Qi Zhang, Tingbo Liang, Wolfgang Schamel, Haopeng Wang, Weiwei Yang, Guangchuan Wang, Zheng-jiang Zhu, Bao-Liang Song, Chenqi Xu
Journal: Cancer Cell (2023)
The regulatory role of PI3K in ageing-related diseases
Authors: Yanqing Liu, Qiong Liu, Zhe Zhang, Yaru Yang, Yazhe Zhou, Huanle Yan, Xin Wang, Xiaoru Li, Jing Zhao, Jingyan Hu, Shulin Yang, Yifan Tian, Yu Yao, Zhenye Qiu, Yanbin Song, Yang Yang
Journal: Ageing Research Reviews (2023)
Helicobacter pylori Burden in the United States According to Individual Demographics and Geography: A Nationwide Analysis of the Veterans Healthcare System
Authors: Shailja C. Shah, Alese E. Halvorson, David Lee, Ranier Bustamante, Brandon McBay, Rohan Gupta, Jason Denton, Chad Dorn, Otis Wilson, Richard Peek, Samir Gupta, Lin Liu, Adriana Hung, Robert Greevy, Christianne L. Roumie
Journal: Clinical Gastroenterology and Hepatology (2023)
Integrins in cancer: Emerging mechanisms and therapeutic opportunities
Authors: Fangfang Liu, Qiong Wu, Zigang Dong, Kangdong Liu
Journal: Pharmacology & Therapeutics (2023)

Integrins are vital surface adhesion receptors that mediate the interactions between the extracellular matrix (ECM) and cells and are essential for cell migration and the maintenance of tissue homeostasis. Aberrant integrin activation promotes initial tumor formation, growth, and metastasis. Recently, many lines of evidence have indicated that integrins are highly expressed in numerous cancer types and have documented many functions of integrins in tumorigenesis. Thus, integrins have emerged as attractive targets for the development of cancer therapeutics. In this review, we discuss the underlying molecular mechanisms by which integrins contribute to most of the hallmarks of cancer. We focus on recent progress on integrin regulators, binding proteins, and downstream effectors. We highlight the role of integrins in the regulation of tumor metastasis, immune evasion, metabolic reprogramming, and other hallmarks of cancer. In addition, integrin-targeted immunotherapy and other integrin inhibitors that have been used in preclinical and clinical studies are summarized.
Learning from serosurveillance for SARS-CoV-2 to inform pandemic preparedness and response
Authors: Sophie A Müller, Ambrose Agweyu, Olusola A Akanbi, Mary A Alex-Wele, Kokou N Alinon, Rahul K Arora, Saidou Balam, Bernard Barekye, Amen Ben Hamida, Isabel Bergeri, Nicki Boddington, Lena Böff, Idesbald Boone, Andelé Conradie, Anahit Demirchyan, Sandra Dudareva, Charbel El Bcheraoui, Megan Evans, Elise Farley, Iris Hunger, Jefferson M Jones, E Wangeci Kagucia, Makobu Kimani, Hannah C Lewis, Festo Mazuguni, Solomon Mwakasungula, Jason M Mwenda, Olena Nesterova, Emmanuel Nepolo, Natasha Nghitukwa, James Nyagwange, Ruth Offergeld, Tochi J Okwor, Felix Reichert, Serine Sahakyan, Sabah Shaikh, Kaveto A Sikuvi, Sabrina Weiss, Mairead Whelan, Christian H Winter, Abdhalah K Ziraba, Johanna Hanefeld
Journal: The Lancet (2023)
The relative contribution of mechanical stress and systemic processes in different types of osteoarthritis: the NEO study
Authors: A W Visser, R de Mutsert, S le Cessie, M den Heijer, F R Rosendaal, M Kloppenburg
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To study the relative contribution of surrogates for mechanical stress and systemic processes with osteoarthritis (OA) in weight-bearing and non-weight-bearing joints. <h3>Methods</h3> The Netherlands Epidemiology of Obesity study is a population-based cohort including 6673 participants (range 45–65 years, 56% women, median body mass index 26 kg/m<sup>2</sup>). Weight (kg) and fat mass (kg) were measured, fat-free mass (kg) was calculated. The metabolic syndrome was defined following the Adult Treatment Panel III criteria. Knee and hand OA were defined according to the American College of Rheumatology clinical criteria. Logistic regression analyses were performed to associate surrogates for mechanical stress (such as weight, fat-free mass) and systemic processes (such as metabolic syndrome) with OA in knees alone, knees and hands or hands alone, adjusted for age, sex, height, smoking, education and ethnicity, and when appropriate for metabolic factors and weight. <h3>Results</h3> Knee, knee and hand, and hand OA were present in 10%, 4% and 8% of the participants, respectively. Knee OA was associated with weight and fat-free mass, adjusted for metabolic factors (OR 1.49 (95% CI 1.32 to 1.68) and 2.05 (1.60 to 2.62), respectively). Similar results were found for OA in knees and hands (OR 1.51 (95% CI 1.29 to 1.78) and 2.17 (95% CI 1.52 to 3.10) respectively). Hand OA was associated with the metabolic syndrome, adjusted for weight (OR 1.46 (95% CI 1.06 to 2.02)). <h3>Conclusions</h3> In knee OA, whether or not in co-occurrence with hand OA, surrogates for mechanical stress are suggested to be the most important risk factors, whereas in hand OA alone, surrogates for systemic processes are the most important risk factors.